Global food and nutritional insecurities, public health challenges of diet-linked non-communicable chronic diseases (NCDs), and rapid climate change-linked agricultural production challenges are interconnected and require urgent attention. Therefore, to address these complex and interconnected challenges, it is essential to advance robust and resilient strategies based on sustainable agricultural production practices, wider integration of nutritionally-balanced plant-based foods in the diet, improvement of human health-targeted nutritional qualities, post-harvest preservation qualities and food processing optimization. Therefore, food plants that are climate resilient and rich source of human health protective nutritional bioactives, such as sweet potato are ideal dietary targets for advancing global food and nutritional security solutions, while also addressing emerging NCD-linked health challenges. Sweet potatoes are rich source of stress protective phenolic bioactives with dual functional benefits relevant for resilience to climate change and countering diet-linked NCD challenges. However, the phenolic bioactive compounds and associated health protective functionalities of sweet potatoes vary widely between different flesh color and cultivars, due to different pre-harvest production practices, post-harvest storage conditions, and with different food processing strategies. Therefore, the aim of this dissertation was to screen sweet potato cultivars of different flesh color (off-white, orange, purple) and optimizing different food processing strategies based on optimum phenolic bioactive-linked antioxidant, anti-diabetic and anti-hypertensive properties using metabolically-targeted in vitro assay models. Overall, high soluble phenolic-linked antioxidant activity was observed in purple-fleshed cultivar, while high type 2 diabetes relevant anti-hyperglycemic and anti-hypertensive properties were observed in orange and white-fleshed sweet potatoes. Additionally, improvement in stability and retention of phenolic bioactives and associated functionalities were present in bio-transformed sweet potatoes after fermentation with beneficial lactic acid bacteria (LAB). Furthermore, food processing (deep-frying, baking, steaming, and boiling) optimization studies revealed optimum food processing conditions (cooking temperature, cooking time, and sweet potato sample size) based on higher retention of phenolics and associated antioxidant and anti-hyperglycemic functionalities. We also advanced metabolically-driven elicitation strategy based on the conceptual foundation of dual functional benefits of phenolic compounds to improve wound-healing in bruised potato tubers through stimulation of redox-linked pathway (pentose phosphate pathway) regulation associated with stress-protective phenolic biosynthesis and antioxidant enzyme responses.